The reversion frequencies of most genetically-altered bacterial pathogens preclude their use as live vaccines. We propose to solve this problem by introducing multiple mutations of identical phenotype into a single strain. The reversion frequency of such a strain will be the product of the reversion rates of the individual mutations. Hence, reversion rates of 10-21 can be achieved, making the strain safe. We have demonstrated the feasibility of this approach by constructing a strain of Haemophilus influenzae with three temperature-sensitive mutations of identical phenotype. We plan to exploit this technology and construct a number of H. influenzae type b strains with vaccine potential and evaluate their efficacy experimental animals.